The histogenesis of carcinoma of the pancreas will be studied and compared in man and experimental animals. The epidemiology of association of putative preneoplastic lesions of human pancreas with risk factors will be analyzed to assess the significance of focal acinar cell dysplasia in human pancreas. One hundred human pancreatic cancers will be studied by electron microscopy to search for evidence of ductal vs. acinar cell origin. The reversibility of carcinogen-induced foci of atypical acinar cells will be assessed in rats. One hundred azaserine-induced pancreatic carcinomas will be classified histologically and compared to the histologic types of human pancreatic cancer. The histogenesis and histologic types of pancreatic cancers will be studied in a single species which responds to carcinogens which are reported to affect acinar cells, i.e. azaserine or N delta-(N-methyl-N-nitrosocarbamoyl)-L-ornithine, and ductal cells, i.e. N-nitrosobis(2-oxopropyamine. Species to be used for these studies are Mastomys natalensis and the Syrian golden hamster. RIA and immunohistochemical demonstration of pancreatic trypsin inhibitors will be employed to study their possible role in inhibition of carcinogenesis in pancreatic acinar cells. The response of transplantable acinar cell and ductal carcinomas of the pancreas to amino acid chemotherapeutic agents will be studied in rats and hamsters.